Safety 143 items
Blood pressure, aldosterone and the organ-system record the class must answer for.
Trials, agents, guidance
- Agent Anacetrapib
- Agent Torcetrapib
- Trial ILLUMINATE
Studies
- The ILLUMINATE trial halts torcetrapib development after finding a 58 percent rise in death from any cause despite a 72 percent HDL cholesterol increase (N Engl J Med 2007)
- REVEAL extended follow-up: the coronary benefit of anacetrapib grows over time, 12% overall, with no long-term safety signal (Eur Heart J 2022)
- Genetic CETP deficiency, mimicking a lifetime of CETP inhibition, trades a lower cardiovascular death and MI risk for a matching rise in AMD (JAMA Cardiol 2022)
- Landmark NEJM safety trial shows anacetrapib avoids the cardiovascular harm of torcetrapib while doubling HDL cholesterol (N Engl J Med 2010)
- Human CETP overexpression in hypertensive Dahl rats spontaneously causes combined hyperlipidemia, myocardial infarction and reduced survival, proving CETP can be proatherogenic (Nat Med 1999)
- Mendelian randomization finds CETP inhibition uniquely associated with increased breast cancer risk among lipid-lowering drug targets (Cancer Causes Control 2024)
- Large Chinese biobank study finds genetically lower CETP activity raises HDL cholesterol but not vascular protection (JAMA Cardiol 2018)
- CETP variants that raise HDL cholesterol also increase risk of intracerebral haemorrhage (Ann Neurol 2016)
- Dal-VESSEL trial finds dalcetrapib cut CETP activity 56% without harming endothelial function or blood pressure (Eur Heart J 2012)
- Discovery paper introduces evacetrapib, a potent CETP inhibitor that raises HDL cholesterol without inducing aldosterone or raising blood pressure (J Lipid Res 2011)
- The ILLUSTRATE trial finds coronary atheroma regression on torcetrapib only in patients reaching the highest quartile of HDL-C rise (Circulation 2008)
- Pooled RADIANCE trial data link the carotid-thickening harm of torcetrapib to a mineralocorticoid effect, not to its HDL-raising action (Circulation 2008)
- First-in-class phase I trials show anacetrapib raises HDL-C by 129% and lowers LDL-C by 38% without raising blood pressure (Lancet 2007)
- The RADIANCE 2 trial finds torcetrapib raises blood pressure and HDL but does not slow carotid thickening in mixed dyslipidaemia (Lancet 2007)
- The ILLUSTRATE trial finds no significant slowing of coronary atheroma progression from torcetrapib despite reaching an LDL-to-HDL ratio below 1.0 (N Engl J Med 2007)
- The RADIANCE 1 trial finds torcetrapib worsens common carotid thickening in familial hypercholesterolemia despite raising HDL to 81.5 mg per dL (N Engl J Med 2007)
- Genetically proxied CETP inhibition increases AMD risk in Mendelian randomization (Ophthalmology 2026)
- A meta-analysis of 62,565 patients confirms CETP inhibitors raise HDL cholesterol by 130 percent yet still fail to reduce cardiovascular events (J Cardiovasc Pharmacol 2026)
- Post hoc BROADWAY/BROOKLYN analysis: obicetrapib attenuates kidney function decline, tracking with achieved HDL-C (Am J Prev Cardiol 2026)
- Pooled phase 3 safety data on 2,880 patients show obicetrapib matches placebo for adverse events, with no blood pressure signal (Am J Prev Cardiol 2026)
- Network meta-analysis of 2,937 patients: obicetrapib outperforms anacetrapib on LDL-C, HDL-C and overall adverse events (Daru 2026)
- Mendelian randomization finds genetically proxied CETP inhibition sharply raises the risk of primary Sjögren's syndrome (Curr Pharm Biotechnol 2026)
- Mendelian randomization finds genetically proxied CETP inhibition reduces sepsis-related critical care admission and death (World J Emerg Med 2025)
- First meta-analysis of nine CETP-inhibitor RCTs finds a class-wide reduction in cardiovascular mortality and myocardial infarction (J Cardiovasc Dev Dis 2024)
- Genetic evidence suggests the HDL cholesterol-sepsis association is not causally mediated through CETP (Clin Transl Sci 2023)
- Meta-analysis of nearly 13,000 patients confirms evacetrapib lowers LDL-C by 34 mg/dL and raises HDL-C substantially (Prostaglandins Leukot Essent Fatty Acids 2021)
- Genetic variants at the CETP inhibitor target show split effects on ischaemic small vessel stroke and brain haemorrhage (Brain 2020)
- JACC review: four CETP inhibitors reached phase 3, one died, two were stopped for futility, and the survivor was shelved over fat accumulation (J Am Coll Cardiol 2019)
- Meta-analysis of 34,781 patients confirms the lipid benefits of anacetrapib carry no excess hepatic or muscular risk (Postgrad Med 2018)
- A proteomic risk score could have flagged harm from torcetrapib within 3 months of ILLUMINATE, revealing unexpected immune and inflammatory effects (Circulation 2018)
- Anacetrapib impairs endothelial function in CETP-transgenic mice despite raising HDL-C fivefold, while evacetrapib does not (Atherosclerosis 2017)
- CETP inhibitors raise blood pressure through a CETP-independent, redox- and STAT3-dependent vascular contraction pathway (J Pharmacol Exp Ther 2016)
- CETP inhibitors trigger aldosterone-producing enzymes in adipocytes through Nox-driven reactive oxygen species and STAT3 (J Pharmacol Exp Ther 2015)
- BMJ meta-analysis of 117,411 patients finds niacin, fibrates, and CETP inhibitors do not reduce mortality on top of statins (BMJ 2014)
- Two more years of anacetrapib in the DEFINE extension sustain a 39.9% LDL-C drop and 153.3% HDL-C rise with no new safety signals (J Cardiovasc Pharmacol Ther 2014)
- Meta-analysis of 12 trials finds CETP inhibitors raise HDL-c by 20.5 mg/dL and lower LDL-c by 17.1 mg/dL, with a blood-pressure signal from torcetrapib (PLoS One 2013)
- The excess mortality and cardiovascular harm of torcetrapib were confined to the low-dose atorvastatin subgroup in ILLUMINATE (J Lipid Res 2012)
- Framingham study finds plasma CETP activity has only minimal association with blood pressure change over time (J Hypertens 2011)
- L-type calcium channels explain how torcetrapib raises aldosterone and blood pressure, an effect dalcetrapib does not share (J Hypertens 2010)
- People with genetically reduced CETP levels have lower, not higher, blood pressure, arguing against a CETP class effect behind the hypertension seen with torcetrapib (Mayo Clin Proc 2010)
- Torcetrapib impairs blood vessel dilation through a mechanism unrelated to CETP inhibition or HDL elevation, unlike a structurally different CETP inhibitor (J Cardiovasc Pharmacol 2010)
- Torcetrapib induces adrenal aldosterone and cortisol via intracellular calcium signaling, unrelated to CETP inhibition (Endocrinology 2009)
- CETP gene variants that raise HDL cholesterol actually lower diastolic blood pressure, arguing the hypertension seen with torcetrapib is compound specific (Pharmacogenet Genomics 2008)
- Adrenalectomy prevents the torcetrapib blood pressure rise, proving CETP inhibition itself is not the culprit (Br J Pharmacol 2008)
- Meta-analysis of three RCTs in 3,286 patients confirms obicetrapib effects on LDL-C, apoB and HDL-C with no excess adverse events (Ann Med Surg 2026)
- Meta-analysis of 3,088 patients: obicetrapib cuts LDL-C by 32% and Lp(a) by 36% with no excess adverse events (Vasc Dis 2026)
- Proteomics plus Mendelian randomisation could have flagged the blood-pressure toxicity of torcetrapib before ILLUMINATE, a proof-of-concept analysis argues (medRxiv preprint 2025)
- Mendelian randomization links the LDL-lowering effect of CETP to reduced obstructive sleep apnea risk (Toxicol Appl Pharmacol 2024)
- Mendelian randomisation flags genetically proxied CETP inhibition as associated with higher male infertility risk, partly via vitamin D (Front Endocrinol 2024)
- CETP variant rs5882 carries a 25-fold higher risk of atrophic age-related macular degeneration in a Lithuanian case-control study (Mol Genet Genomic Med 2020)
- CETP promoter variant rs1800775 reduces the odds of essential hypertension in a Mexican population (Genet Test Mol Biomarkers 2020)
- Unlike torcetrapib, evacetrapib left plasma aldosterone unchanged in ACCELERATE, and aldosterone did not predict cardiovascular events (J Am Heart Assoc 2019)
- Anacetrapib parks itself in the lipid droplets of fat cells without needing active transport, explaining its long half-life and shelving (Drug Metab Dispos 2019)
- Human phase 1 data confirm anacetrapib keeps accumulating in fat for a year while plasma levels plateau, explaining its long residence time (Clin Pharmacol Ther 2017)
- Mendelian randomization finds HDL-raising CETP variants also raise the risk of age-related macular degeneration (Ophthalmology 2017)
- Rabbit developmental study finds the offspring-survival NOAEL for evacetrapib is a third of the maternal NOAEL (Birth Defects Res 2017)
- High-dose evacetrapib causes toxicity in parent rats but leaves fertility and fetal development unharmed in rats and rabbits (Birth Defects Res 2017)
- Torcetrapib raised HDL ApoC-III and LpA-I subclasses without altering ApoB particles in ILLUMINATE (Am J Cardiol 2017)
- Review details how evacetrapib raised HDL-C by 128% and cut LDL-C by 35% yet produced no clinical benefit in ACCELERATE (Cardiol Rev 2017)
- Phase 1 single ascending dose study of the CETP inhibitor CKD-519 shows potent target inhibition (Drug Des Devel Ther 2016)
- Meta-analysis finds evacetrapib raises HDL-C by 86% and cuts LDL-C by 21%, with no effect on triglycerides (Curr Pharm Des 2016)
- Less lipophilic hexahydrofuroquinoline CETP inhibitor clears fat tissue quickly and avoids off-target hypertension signals (J Med Chem 2014)
- Meta-analysis of 69,515 patients finds niacin and CETP inhibitors do not reduce cardiovascular mortality (Nutr Metab Cardiovasc Dis 2015)
- At the highest dose, evacetrapib inhibits CETP by 91% and raises HDL-C by 87% without moving 24-hour blood pressure (J Pharm Pharmacol 2014)
- Even at 8 times the therapeutic dose, anacetrapib does not clinically prolong the QTcF interval (J Clin Pharmacol 2014)
- A thorough QT study finds evacetrapib safe on cardiac rhythm even at 5-fold the exposure planned for phase 3 (J Cardiovasc Pharmacol Ther 2014)
- Network pharmacology points to PDGFR, HGFR, and IL-2 receptor as possible off-target drivers of the cardiovascular harm from torcetrapib (BMC Syst Biol 2012)
- Unlike torcetrapib, dalcetrapib, evacetrapib, and anacetrapib do not raise blood pressure or aldosterone (Curr Opin Lipidol 2012)
- DEFINE trial found anacetrapib safe through 76 weeks with no signal for the 25% event excess seen with a prior CETP inhibitor (Expert Rev Cardiovasc Ther 2012)
- Review distills lessons from the torcetrapib failure for the CETP inhibitors that followed it into clinical development (Curr Clin Pharmacol 2012)
- First-in-human single dose study of the CETP inhibitor BAY 60-5521 shows dose-dependent CETP inhibition and HDL rise (Br J Clin Pharmacol 2012)
- Sirtori weighs the cancer and sepsis signals of torcetrapib against the dramatic 139% HDL rise seen with anacetrapib (Expert Opin Investig Drugs 2011)
- Torcetrapib impairs endothelial function and raises vascular oxidative stress in hypertensive rats, reversed by endothelin blockade (Eur Heart J 2012)
- CETP concentration is higher in coronary heart disease patients but is not itself an independent predictor of LDL particle size (Bosn J Basic Med Sci 2011)
- Doses of dalcetrapib up to 4500 mg, far above the therapeutic dose, are well tolerated in a phase I ascending-dose study (Clin Drug Investig 2011)
- Review argues CETP may be atheroprotective and aid host defense, complicating the case for inhibiting it (Cardiovasc Ther 2011)
- A 48-week trial finds dalcetrapib raises HDL cholesterol by a third with no measurable effect on lymph node size (Eur Heart J 2010)
- Torcetrapib raises blood pressure in dogs through systemic and pulmonary vasoconstriction that also strains the heart (J Cardiovasc Pharmacol 2009)
- Torcetrapib raises blood pressure and RAAS gene expression in rats, but dalcetrapib does neither (Br J Pharmacol 2009)
- Barter reflects on ILLUMINATE: the harm caused by torcetrapib likely reflects off-target effects, not CETP inhibition itself (Am J Cardiol 2009)
- Multiple-dose study of the CETP inhibitor CP-800,569 shows dose-dependent HDL rise and LDL fall (Clin Pharmacol Ther 2009)
- Pooled phase II data show dalcetrapib raises HDL cholesterol up to 36 percent without the blood pressure or aldosterone effects seen with torcetrapib (Am J Cardiol 2009)
- Hegele argues the pressor effect of torcetrapib, not CETP inhibition itself, doomed the drug and asks if the class deserves another chance (Curr Opin Cardiol 2009)
- Torcetrapib and CP-532,623 raise blood pressure via a chemotype-specific mechanism dissociated from CETP inhibition timing (J Cardiovasc Pharmacol 2009)
- Natural variation in plasma CETP levels does not affect RAAS responsiveness or blood pressure reactivity in healthy men (Expert Opin Ther Targets 2008)
- Torcetrapib produces smaller but more inflamed, less stable plaques than atorvastatin in humanized transgenic mice (Circulation 2008)
- Review questions whether CETP inhibitors remain a viable therapeutic approach after a major trial failure (Cardiovasc Ther 2008)
- A review proposes that the now-known crystal structure of CETP could guide the design of inhibitors that avoid the nonproductive HDL complex formed by torcetrapib (Am J Cardiol 2007)
- A review says the CETP crystal structure could enable inhibitors that avoid the nonproductive HDL-binding complex formed by torcetrapib (Curr Opin Cardiol 2007)
- CETP TaqI B1B2 genotype triples hypertension risk in North Indian diabetics despite no direct T2DM link (BMC Endocr Disord 2005)
- Phase 1 trial finds a CETP vaccine induces anti-CETP antibodies and is well tolerated in healthy adults (Atherosclerosis 2003)
- Obicetrapib plus ezetimibe reduces LDL-C by 49.15 percent in a network meta-analysis (Endocrinol Diabetes Metab 2026)
- Obicetrapib achieves up to 97% CETP inhibition and reduces LDL cholesterol by 30-50% across phase I-III trials (Eur Cardiol 2026)
- A CETP variant is significantly associated with pentosan polysulfate (Elmiron) maculopathy, a genetic study of a drug-induced retinal disease finds (Retina 2023)
- Walnut supplementation as a statin adjuvant lowers CETP activity and raises HDL cholesterol in hypertensive patients (Clin Exp Hypertens 2022)
- Anacetrapib pharmacokinetics in healthy Chinese subjects closely match those seen in black and white populations (Adv Ther 2021)
- In hypertensive rats made to express human CETP, blood pressure rose and fatty liver accelerated, yet atherosclerosis did not (Hypertens Res 2020)
- CETP TaqIB genotype shapes how plant oils affect metabolic markers in people with diabetes (J Cardiovasc Thorac Res 2020)
- Anacetrapib accumulates to 0.6 mmol/L in mouse adipose tissue without impairing adipose function, even after weight loss (Pharmacol Res Perspect 2019)
- Lead triphenylethanamine CETP inhibitor shows clean blood pressure profile and robust efficacy (ACS Med Chem Lett 2019)
- High-dose PFOA raises HDL cholesterol by suppressing cholesteryl ester transfer activity in mice (Toxicol Sci 2019)
- A review of dalcetrapib pharmacokinetics finds no clinically significant drug interactions across over 13,000 patients and volunteers (Clin Pharmacokinet 2018)
- Meta-analysis identifies two CETP variants among the leading genetic risk factors for polypoidal choroidal vasculopathy in Asians (J Ophthalmol 2018)
- In 1,264 Lithuanians, two CETP variants raise exudative AMD risk up to 1.7-fold while a third, rs3764261, cuts it by 1.8-fold (Gene 2017)
- A protective CETP haplotype, but not individual TaqIB or D442G variants, lowers essential hypertension risk in Chinese Mongolians (Turk J Med Sci 2017)
- Policosanol supplementation reduced CETP activity by up to 32% and lowered blood pressure in healthy adults (Int J Mol Med 2017)
- Severe hepatic impairment, but not severe renal impairment, raises evacetrapib exposure and prolongs its half-life (Eur J Clin Pharmacol 2016)
- Neither moderate hepatic nor severe renal impairment meaningfully alters anacetrapib pharmacokinetics (J Clin Pharmacol 2014)
- Unlike torcetrapib, anacetrapib raises HDL-C by 138% without elevating blood pressure or disturbing electrolytes (Cardiol Rev 2014)
- The weight-loss drug orlistat cuts exposure to active dalcetrapib by more than half by blocking its ester hydrolysis (J Cardiovasc Pharmacol 2012)
- Anacetrapib has no clinically meaningful interaction with warfarin, sparing patients a dosage adjustment (Br J Clin Pharmacol 2012)
- Optimised DPPE-derivative CETP inhibitor shows robust efficacy without raising blood pressure in telemetered rats (J Med Chem 2012)
- Review profiles the early safety advantage of evacetrapib over torcetrapib as cardiovascular outcomes remain unknown (Curr Cardiol Rep 2012)
- Torcetrapib raises blood pressure across four independent cardiovascular models, validating them as predictive lead-optimization tools (J Cardiovasc Pharmacol 2012)
- Liver tumors seen in a 2-year mouse study of dalcetrapib trace to a rodent-specific pathway not relevant to humans (Toxicol Appl Pharmacol 2012)
- A review of biomarker and imaging trials shows the favorable lipid effects of torcetrapib failed to predict a 58 percent rise in mortality (Can J Cardiol 2012)
- Anacetrapib does not meaningfully inhibit P-glycoprotein, leaving digoxin exposure essentially unchanged (Biopharm Drug Dispos 2011)
- Review traces the ILLUMINATE mortality signal of torcetrapib to adrenal aldosterone secretion, not receptor blockade (Hypertens Res 2010)
- Noninvasive high-definition oscillometry matches implanted telemetry for tracking torcetrapib-induced blood pressure rises in dogs (J Am Assoc Lab Anim Sci 2010)
- Even at more than 6 times the therapeutic dose, dalcetrapib does not prolong the QT interval in healthy subjects (Eur J Clin Pharmacol 2010)
- The rodent-specific scavenger receptor MARCO drives the off-target lipid uptake seen with dalcetrapib in mouse macrophages (Toxicol In Vitro 2010)
- A review argues the mortality signal from torcetrapib traces to off-target toxicity, not to CETP inhibition itself (Am J Cardiol 2009)
- Torcetrapib does not block CETP or LPS-binding-protein interactions, ruling out a direct sepsis-mortality mechanism (J Lipid Res 2010)
- A translational-medicine commentary argues the failure of 4 large torcetrapib trials calls for biomarker-driven drug development, not abandonment of CETP as a target (Biochem Pharmacol 2009)
- A review draws lessons from ILLUMINATE on the hypertension risk of CETP inhibitors despite raising HDL cholesterol by up to 100 percent (Curr Hypertens Rep 2009)
- A review concludes the mineralocorticoid-driven hypertension seen with torcetrapib is not a CETP-inhibitor class effect, since JTT-705 and MK-825 do not raise blood pressure (Nat Clin Pract Cardiovasc Med 2008)
- A review questions whether CETP inhibitors can ultimately reduce cardiovascular events after torcetrapib raised blood pressure without slowing coronary atherosclerosis (Am J Cardiol 2007)
- Adding bezafibrate to long-term probucol therapy can trigger severe HDL and apolipoprotein A-I deficiency (Eur J Clin Pharmacol 1995)
- Preclinical safety battery clears the anti-CETP intranasal vaccine HB-ATV-8 for cardiac, mutagenic and metabolic risk (Arch Med Res 2026)
- A review of nonstatin add-on therapies finds torcetrapib raised mortality in coronary patients despite a marked rise in HDL cholesterol (Curr Atheroscler Rep 2009)
- A review attributes the excess deaths seen with torcetrapib to an off-target effect, not to CETP inhibition, while low HDL remains an important risk marker (Curr Opin Endocrinol Diabetes Obes 2008)
- A post hoc review of the safety monitoring board for the torcetrapib trial warns against over-relying on formal statistical stopping rules (Eur J Clin Pharmacol 2008)
- Hypothesis paper proposes that the ILLUMINATE deaths from torcetrapib trace to eNOS inhibition via HDL-SR-BI signaling loss (Med Hypotheses 2007)
- Alcohol abuse alters CETP glycosylation, lowering its surface charge and likely its activity (Alcohol Alcohol 2006)
- Walnut kernel polyphenols are proposed to improve metabolic syndrome partly by inhibiting SREBPs, PCSK9 and CETP (Food Sci Nutr 2024)
- Saccharin-fed zebrafish show elevated CETP activity while aspartame-fed zebrafish suffer acute deaths under high-cholesterol diet (Food Chem Toxicol 2011)
- AHA 2010 trials update reports DEFINE found no adverse safety signal for anacetrapib (Cardiovasc Drugs Ther 2011)
- The dal-VESSEL study is designed as the largest trial of brachial flow-mediated dilatation to test dalcetrapib effects on endothelial function (Curr Med Res Opin 2011)
- Single endotoxin dose triggers rapid LDL decline and slower CETP activity loss in healthy volunteers (J Lipid Res 2003)